This application requests funding for a state-of-the-art shared hybrid mass spectrometer that will provide collaborative research and core service usage for the Yale University, W.M. Keck Biotechnology Resource Laboratory's MS & Proteomics Core. The LTQ-Orbitrap hybrid mass spectrometer manufactured by Thermo Fisher Scientific combines a linear quadrupole ion-trap with the orbitrap mass spectrometer. When this requested mass spectrometer is utilized with our in-house developed phosphopeptide enrichment methodologies and an existing, "inert" capillary nano scale HPLC system, the resulting platform and the applied methodologies will provide what we believe to be the first robust, dedicated phosphoprotein profiling and related phosphoproteomics services available from a major academic core facility. The LTQ-Orbitrap mass spectrometry platform has a unique, MS2 and MS3 data dependent phosphopeptide acquisition capability that is tightly coupled with robust, highly sensitive, fast scanning, high resolution, high mass accuracy, and wide dynamic range characteristics that together create an unmatched ability to confidently detect and identify large numbers of phosphopeptides from highly complex, digested cell and tissue protein extracts of interest. In addition, the platform also offers detection and identification of other protein post-translational modifications, lipids, metabolites, and other types of analyses not currently offered by the Keck Laboratory. Because of these unique capabilities and the important role that phosphorylation plays in controlling protein function, there is very strong interest in providing the Keck Laboratory with this platform so it can be made available on a service charge basis to support 33 biomedical research projects overseen by 26 major and five minor users from 13 universities and medical centers. These users include members of four NIH Centers that are closely associated with the Keck Laboratory and that have strong proteomics components (i.e., Yale/NHLBI Proteomics Center, Yale/NIDA Neuroproteomics Center, the Proteomics Shared Resource in the NCI-funded Yale Cancer Center, and the Proteomics Core of the NIAID-funded Northeast Center of Excellence for Biodefense). Two of the major users, Richard Lifton (NHLBI) and Angus Nairn (NIDA), will collaborate with our center to pursue their research applications in renal disease and in drug addiction and depression while also collaborating on biotechnology research directed at further advancing our highly promising phosphoproteomics technologies. This effort will then serve as the basis for rapidly developing new phosphoproteomics services that will be made available to all other research contributors and users of the Keck Laboratory. [unreadable] [unreadable] Relevance: If this grant is funded, the LTQ-Orbitrap system would make a unique contribution to biomedical research that would extend to investigators studying fundamental mechanisms of diseases including schizophrenia, depression, substance abuse, preterm birth, asthma, melanoma, renal diseases, and the effects of biodefense related microbial pathogens such as anthrax. [unreadable] [unreadable] [unreadable]